Rhodanine-Sulfonate hybrids targeting aldose reductase: Synthesis, in vitro inhibition, molecular docking, and cytotoxicity studies

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dc.authorid0000-0002-1330-6194
dc.contributor.authorKalay, Erbay
dc.contributor.authorDemir, Yeliz
dc.contributor.authorTurkes, Cuneyt
dc.contributor.authorAslan, Osman Nuri
dc.contributor.authorPezik, Esra
dc.contributor.authorSahin, Engin
dc.date.accessioned2026-02-28T12:17:42Z
dc.date.available2026-02-28T12:17:42Z
dc.date.issued2025
dc.departmentBayburt Üniversitesi
dc.description.abstractAldose reductase (ALR2), a key enzyme in the polyol pathway, plays a significant role in the onset and progression of diabetic complications, rendering it a critical pharmacological target. In this study, a novel series of twenty-four sulfonate ester-functionalized rhodanine derivatives (compounds 1-24) were rationally designed, synthesized via Knoevenagel condensation, and comprehensively evaluated for their inhibitory activity against ALR2. Spectroscopic and spectrometric methods confirmed the structural integrity of the synthesized compounds. In vitro enzyme inhibition assays revealed that all compounds acted as competitive inhibitors, with several analogues, particularly compounds 6 and 8, exhibiting stronger ALR2 inhibition (Ki = 0.43 mu M and 0.48 mu M, respectively) than the reference drug epalrestat (Ki = 0.98 mu M). Structure-activity relationship (SAR) analysis highlighted the critical influence of para-substituted electron-donating (e.g., methyl) and electron-withdrawing (e.g., nitro, halogen) groups on binding potency. Molecular docking of the most potent inhibitor (compound 6) demonstrated a stable binding pose supported by key interactions, including hydrogen bonding with His110 and pi-pi stacking with Phe122. In silico ADME profiling confirmed favorable drug-likeness properties for all derivatives. Cytotoxicity studies on L929, A549, and RG-2 cell lines revealed that most compounds were less toxic than the reference drug at lower concentrations, with compound 8 showing a promising cytotoxic profile. These findings position rhodanine-sulfonate hybrids as promising scaffolds for the development of next-generation ALR2 inhibitors for the treatment of diabetic complications.
dc.description.sponsorshipUnit of Scientific Research Projects of University of Ardahan [2023-004]
dc.description.sponsorshipThis research was supported by the Unit of Scientific Research Projects of University of Ardahan [Grant number: 2023-004].
dc.identifier.doi10.1007/s11030-025-11387-0
dc.identifier.issn1381-1991
dc.identifier.issn1573-501X
dc.identifier.pmid41196472
dc.identifier.scopus2-s2.0-105021102239
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1007/s11030-025-11387-0
dc.identifier.urihttps://hdl.handle.net/20.500.12403/5938
dc.identifier.wosWOS:001610562300001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofMolecular Diversity
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WoS_20260218
dc.subjectRhodanine
dc.subjectSulfonate ester
dc.subjectAldose reductase
dc.subjectCytotoxicity
dc.subjectMolecular docking
dc.titleRhodanine-Sulfonate hybrids targeting aldose reductase: Synthesis, in vitro inhibition, molecular docking, and cytotoxicity studies
dc.typeArticle

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